(ne faz' oh done hye'' droe klor' ide).
3H-1,2,4-Triazol-3-one, 2-[3-[4-(3-chlorophenyl)-1-piperazinyl)]propyl]-5-ethyl-2,4-dihydro-4-(2-phenoxyethyl)-, monohydrochloride;
1-[3-[4-(m-Chlorophenyl)-1-piperazinyl]propyl]-3-ethyl-4-(2-phenoxyethyl)-D2-1,2,4-triazolin-5-one monohydrochloride [82752-99-6].
Nefazodone Hydrochloride contains NLT 98.0% and NMT 102.0% of C25H32ClN5O2·HCl, calculated on the dried basis.
• B. Identification TestsGeneral, Chloride 191: Meets the requirements
Sample solution: 10 mg/mL in methanol
Sample solution: 800 mg of Nefazodone Hydrochloride in 50 mL of glacial acetic acid. Add 15 mL of 3% mercuric acetate in glacial acetic acid.
(See Titrimetry 541.)
Titrant: 0.1 N perchloric acid VS
Endpoint detection: Potentiometric
Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Carry out a blank titration.
Calculate the percentage of C25H32ClN5O2·HCl in the portion of Nefazodone Hydrochloride taken:
Result = ((V B) × N × F/W) × 100
Acceptance criteria: 98.0%102.0% on the dried basis
Diluent: Acetonitrile and water (1:1)
Solution A: 0.77 g/L of ammonium acetate in water.
Adjust with triethylamine to a pH of 7.10 ± 0.05, and degas.
Solution B: Acetonitrile (degassed)
Mobile phase: See the gradient table below.
Impurities stock solution: 0.1 mg/mL of USP Nefazodone Related Compound A RS and USP Nefazodone Related Compound B RS in Diluent
Standard stock solution: 0.1 mg/mL of USP Nefazodone Hydrochloride RS in Diluent
System suitability solution: 5 µg/mL each of USP Nefazodone Related Compound A RS and USP Nefazodone Related Compound B RS from the Impurities stock solution in the Standard stock solution
Standard solution: 1 µg/mL each of Nefazodone Hydrochloride, USP Nefazodone Related Compound A RS, and USP Nefazodone Related Compound B RS from the Standard stock solution and the Impurities stock solution in Diluent
Sample solution: 1 mg/mL of Nefazodone Hydrochloride in Diluent
Detector: UV 250 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 1.7 mL/min
Injection size: 10 µL
Samples: System suitability solution and Standard solution
Resolution: NLT 4.0 between nefazodone related compound A and nefazodone hydrochloride; NLT 1.5 between nefazodone hydrochloride and nefazodone related compound B, System suitability solution
Relative standard deviation: NMT 5.0% for nefazodone related compound A and nefazodone related compound B, Standard solution
Samples: Standard solution and Sample solution
Calculate the percentage of each nefazodone related compound in the portion of Nefazodone Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
[NoteUse the peak area for nefazodone hydrochloride in the Standard solution as rS to calculate any unknown impurity. ]
Individual impurities: See Impurity Table 1.
Total impurities: NMT 0.5%
Impurity Table 1
• Loss on Drying 731: Dry a sample in a vacuum at 105 for 3 h: it loses NMT 0.5% of its weight.
• Completeness of Solution 641: Meets the requirements
Sample solution: 25 mg/mL in methanol
• Packaging and Storage: Preserve in tight containers. Store between 15 and 30.
• USP Reference Standards 11
USP Nefazodone Related Compound A RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4007Pharmacopeial Forum: Volume No. 35(3) Page 540